Red Blood Cell Pathology in Hemodialysis Patients By 2030, estimates predict that over 2 million people in the US will require hemodialysis as a result of end stage renal disease (ESRD). Patients receiving hemodialysis are at high risk for morbidity and mortality from cardiovascular complications. However, vascular access dysfunction, due to thrombosis and stenosis of the arteriovenous grafts, results in more hospitalizations than any other complication in this patient group. Underpinning the coagulation and cardiovascular events in these patients is the presence of profound inflammation and coagulation activation. However, the underlying cause of hyper-inflammation or -coagulation in patients on hemodialysis has yet to be determined. Healthy RBCs are designed to freely and permanently remain in, and sustain, the laminar flow of blood. These cells are strictly non-adhesive and maintain precise membrane asymmetry. If either of these physiological components is lost, the RBC converts into a proinflammatory, pro-coagulatory cell with detrimental and global effects on hemostasis. We have discovered that RBCs are adhesive and have lost membrane symmetry in patients on hemodialysis. Thus both of these physiological components of the RBC are disrupted in these patients.To date, no study has ever sought to examine the role of RBC pathology in inflammation and coagulation in ESRD patients on hemodialysis. We have found that RBCs from these patients are highly adhesive to pro-inflammatory cells in vasculature, and expose the pro-coagulatory lipid phosphatidylserine (PS) on their surface. We have further discovered that factors in the plasma of hemodialysis patients can induce these changes in the RBC. Thus, our data suggest that the RBC in these patients could be a major contributor to both inflammation and coagulation. What we do not know, however, are the mechanisms of RBC adhesion and pathological consequences of such adhesion. We do not know the fundamental changes in the RBC that occur during hemodialysis that allow PS to be exposed or activate such adhesion. Further, we do not know if any of these pathologies correlate to clinical outcome. This study seeks to answer those fundamental questions raised by our novel detection of RBC pathology in these patients. It promises, upon its completion, to open up entirely new avenues of therapy and understanding of inflammation and coagulation in ESRD patients on hemodialysis.